Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative organism of coronavirus disease 2019 (COVID-19), can also affect many extra-respiratory systems.¹ As viral entry into host cells is facilitated by the interaction between the SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2) receptors, many organ systems that express these receptors, including prostate epithelial cells, are potentially susceptible to SARS-CoV-2 direct invasion as well.^1,2 While several small-scale studies reported the worsening of male lower urinary tract symptoms (LUTS) after COVID-19, no large study has examined the urological effects of SARS-CoV-2 infection.¹_­ In the captioned study conducted by researchers from The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine), large-scale real-world data were used to explore the correlation between SARS-CoV-2 infection and benign prostatic hyperplasia (BPH) complications.¹

Benign prostatic hyperplasia (BPH) is one of the most common diseases in aging men and is estimated to impact more than 80% of men above 70 years of age.¹ BPH is characterized by the non-malignant proliferation of stromal and epithelial cells of the prostate, resulting in compression of the urethra and resistance to urine flow.³ BPH can have a considerable effect on the quality of life of patients and can often lead to complications such as retention of urine (ROU), urinary tract infection (UTI), hematuria and bladder stone formation.^1,3 As prostate epithelial cells co-expresses ACE2 and the surface protease TMPRSS2, the male lower urinary tract is a also target for SARS-CoV-2 infection, leading to inflammation which could worsen LUTS.¹ Furthermore, metabolic dysregulation associated with SARS-CoV-2 infection also contributes to chronic systematic inflammation which could exacerbate LUTS.¹ The objective of this study was thus to investigate how SARS-CoV-2 would affect male LUTS associated with BPH using large-scale real-world data.¹

In this retrospective cohort study, data from all male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021-2022 were obtained from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority.¹ After the exclusion of patients with a history of prostate cancer or stone disease in the past 5 years or a history of ROU within 1 year, polymerase chain reaction (PCR) test results for SARS-CoV-2 were extracted from CDARS.¹ Propensity score matching was performed and 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n=8,993) while the remaining patients had no positive PCR test for SARS-CoV-2 (n=8,993).¹ Mean follow-up duration was 54.16 days in the control group and 55.27 days in the SARS-CoV-2 group.¹

Compared to the control group, patients infected with SARS-CoV-2 had significantly higher incidence rates of ROU (4.55% vs. 0.86%; p<0.001), hematuria (1.36% vs. 0.41%; p<0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%; p<0.001), culture-proven bacteriuria (9.02% vs. 1.97%; p<0.001), and addition of 5-alpha reductase inhibitor (5ARI) for combination therapy upon follow-up (0.50% vs. 0.02%; p<0.001).¹ Further analysis suggested that patients with COVID-19 have roughly 5 times the risk of ROU (RR=5.31; 95% CI: 4.17-6.76) and bacteriuria (RR=4.58; 95% CI: 3.90-5.38), and 3 times the risk of hematuria (RR=3.30; 95% CI: 2.29-4.76) and clinical UTI (RR=2.90; 95% CI: 2.38-3.52) compared to patients without.¹

Subgroup analysis stratified by age demonstrated similar differences across most age groups except for younger age groups (<50 years), while the incidences of outcomes of interest were higher in more advanced age groups.¹ While there were no statistically significant differences in the incidence of ROU, hematuria, or 5ARI addition across COVID-19 severities, lower incidence of UTI (p<0.001) or bacteriuria (p<0.001) were found in patients with the least COVID-19 severity (asymptomatic or pre-symptomatic infection).¹

In summary, this cohort study demonstrated the association between SARS-CoV-2 infection and increased incidence of BPH complications in terms of urinary retention, hematuria, UTI, and the addition of combination therapy, regardless of COVID-19 severity.¹ Clinicians should be aware of the significantly higher incidence of LUTS complications in patients with COVID-19 which can be observed even in asymptomatic infection.¹